The Anti-hypertension Effects Of Cardiac κopioid Rector And Its Mechanism

The existence of Endogenous Opioid Peptide (EOP) has been known for a long time, and it has been recognized that EOP has a central paregoric effect and can regulate cardiovascular functions. Most of the past studies focused on its central effects. Now it has been found opioid receptors exist extensively in myocardium vascular wall, and heart can synthesize EOP as well. These findings indicate that EOP may have direct effects on cardiovascular system. In recent years, much attention has been given to the regulatory effects of EOP on cardiovascular system, and studies have found that EOP play a role in the pathogenesis and development of heart diseases.Our study focused on the effects of activating k opioid rector on the cardiovascular system and its probable mechanism, and studied their effects in context of the developing of the hypertension., and tried to discuss the potential clinical value of K. opioid rector agonists in curing the hypertension.The main contents of this study include:1. Investigate the effects of the U50,488H (selective K opioid receptor agonist) on growth of norepinephrine (NE) stimulated cardiac myocytes ofneonatal rats using cell culture and MTT method.2. Investigate the effects of the U50,488H on the isoproterenol (ISO)-induced cardiac hypertrophy model by histopathological study and measuring heart weight.3. With drugs given intravenously, heart rate (HR), arterial blood pressure (ABP), left ventricular pressure (LVP) and 眃p/dtm(K were recorded to observe the negative inotropic effects of U50,488H on hearts of rats.4. By perfusion of isolated rat hearts, we studied the modulatory effects of U50,488H on B - adrenoceptor (P -AR).5. The relaxation effect of U50,488H on abdominal aorta and underlying mechanism in the rat was studied by means of the isolated abdominal aorta perfusion and the tension of the vessel measurement.Main results:1. U50,488H (1-10 u mol ?L"1) , in a dose-dependent way, inhibited the growth of cardiac myocytes stimulated by NE. In MTT assay, OD value of U50, 488H group were lower than those of the NE group.2. U50,488H significantly inhibited the cardiac hypertrophy induced by ISO. U50, 488H could significantly inhibit the myocardiac thickening induced by ISO, rats injected with only isoprenaline showed notably enlarged hearts and marked myocardiac thickening. Pathological changes were found under a microscope including: necrosis of the ventricular muscular cells, extensive fibrosis, generous proliferation of mitochondria in the myocardiac cells, disturbed arrangement of myofliaments, increased amount of cytoplasmic dense particles, and local lysis of myofliaments. However, hearts of rats coadministered with U50,488H showed no apparent enlargement, hypertrophyof the myocardiac cells was much slighter than that of rats treated with isoprenalme only. Under microscope, it was shown that the cardiac muscular fibers were neatly arranged. Necrosis and fibrosis were rarely found, and no significant proliferation of mitochondria was seen. Besides, filaments were relatively regularly arranged compared with the isoprenaline-treated group. The heart weight quotient (heart weight/body weight) of the rats treated with ISO together with U50,488H was lower than ISO-treated group.3. U50,488H (10 u mol ?L'1) can decrease the HR, LVP and ?dp/dtmax in rabbits hearts and isolated rats hearts.4. The effects of ISO were weakened by U50,488H (10 w mol ?L'1) .5. U50,488H (20-100 umol ?I/1) had the significant dose-dependent relaxation effect on rat abdominal aorta; (2)The relaxation effect of U50, 488H on rat abdominal aorta was endothelium-dependent; ㏕he relaxation effect of U50, 488H on rat abdominal aorta was inhibited by presence of glybenclamide; @The relaxation effect of U50, 488H on blood vessel had no relation with M-receptor, P -receptor, prostaglandin and nitric oxide (NO).The above-mentioned results suggest:1. Stimulation of K opioid receptor on heart can significantly inhibit the growth and hypertrophy of car...